The proposed studies use a novel experimental model of viral latency and reactivation that utilizes primary memory cells as targets. Using this system, we plan to understand in detail the mechanisms that HIV-1 uses to establish latency in vivo, as well as the physiological signals that trigger viral reactivation. Knowledge from these areas will be applicable in future translational studies that will seek compounds mimicking or antagonizing the relevant signaling pathways, with the ultimate goal of destroying the latent reservoir.